Chromogranin a immunoreactivity in human cerebrospinal fluid: Properties, relationship to noradrenergic neuronal activity, and variation in neurologic disease

Abstract

Although measurement of chromogranin A in the bloodstream is of value in sympathoadrenal investigations, little is systematically known about chromogranin A in cerebrospinal fluid, despite substantial knowledge about its occurrence and distribution in brain. We therefore applied a homologous human chromogranin A radioimmunoassay to cerebrospinal fluid, in order to evaluate the properties and stability of cerebrospinal fluid chomogranin A, as well as its relationship to central noradrenergic neuronal activity, to peripheral (plasma) chromogranin A, and to disease states such as hypertension, renal failure and Parkinsonism. Authentic, physically stable chromogranin A immunoreactivity was found in cerebrospinal fluid (at 37–146 ng/ml; mean, 87.0 ± 6.0 ng/ml in healthy subjects), and several lines of evidence (including 3.39 ± 0.27-fold higher chromogranin A in cerebrospinal fluid than in plasma) indicated that it originated from a local central nervous system source, rather than the periphery. Cerebrospinal fluid chromogranin A values were not influenced by administration of effective antihypertensive doses of clonidine or propranolol, and were not related to the cerebrospinal fluid concentrations of norepinephrine, methoxyhydroxyphenylglycol, or dopamine-beta-hydroxylase; thus, cerebrospinal fluid chromogranin A was not closely linked to biochemical or pharmacologic indices of central noradrenergic neuronal activity. Cerebrospinal fluid chromogranin A was not changed (P>0.1) in essential hypertension (84.2 ± 14.0 ng/ml) or renal failure (72.2 ± 13.4 ng/ml), despite a marked (7.1-fold; P< 0.001) increase in plasma chromogranin A in renal failure, and a modest (1.5-fold; P=0.004) increase in plasma chromogranin A in essential hypertension. In Parkinson's disease, a diminution (2.8-fold; P< 0.001) of cerebrospinal fluid chromogranin A may be of diagnostic value.